Quantification of renal perfusion abnormalities using an intravascular contrast agent (part 2): results in animals and humans with renal artery stenosis.

The interrelation between the morphologic degree of renal artery stenosis and changes in parenchymal perfusion is assessed using an intravascular contrast agent. In seven adult foxhounds, different degrees of renal artery stenosis were created with an inflatable clamp implanted around the renal artery. Dynamic susceptibility-weighted gradient-echo imaging was used to measure signal-time curves in the renal artery and the renal parenchyma during administration of 1.5 mg/kg BW of an intravascular ultrasmall particle iron oxide (USPIO) contrast agent. From the dynamic series, regional renal blood volume (rRBV), regional renal blood flow (rRBF), and mean transit time (MTT) were calculated. The morphologic degree of stenosis was measured in the steady state using a high-resolution 3D contrast-enhanced (CE) MR angiography (MRA) sequence (voxel size = 0.7 x 0.7 x 1 mm(3)). Five patients with renoparenchymal damage due to long-standing renal artery stenosis were evaluated. In the animal stenosis model, cortical perfusion remained unchanged for degrees of renal artery stenosis up to 80%. With degrees of stenoses > 80%, cortical perfusion dropped to 151 +/- 54 ml/100 g of tissue per minute as compared to a baseline of 513 +/- 76 ml/100 g/min. In the patients, a substantial difference in the cortical perfusion of more than 200 +/- 40 ml/100 g/min between the normal and the ischemic kidneys was found. The results show that quantitative renal perfusion measurements in combination with 3D-CE-MRA allow the functional significance of a renal artery stenosis to be determined in a single MR exam. Differentiation between renovascular and renoparenchymal disease thus becomes feasible.     

Antibakterielle Aktivität von Clindamycin und Linkomycin in Bouillon,Serum und in Kombination mit Polymorphkernigen Granulozyten gegen Staphylococcus aureus und Staphylococcus epidermidis

Zusammenfassung Wir untersuchten die antibakterielle Aktivität von Clindamycin und Linkomycin bei 1/4 × minimaler Hemmkonzentration (=MHK), 1 × MHK und 4 × MHK gegen einen serumresistentenStaphylococcus aureus- und einen serumresistentenStaphylococcus epidermidis-Stamm in Bouillon, in Serum mit und ohne Gegenwart von Leukozyten bzw. in Hank's Medium mit Leukozyten allein. Linkomycin war gegen beide Teststämme in Bouillon und Serum gleichermaßen wirksam, während Clindamycin in Bouillon gegenS. aureus doch etwas aktiver war. Im kombinierten Ansatz von Serum mit Leukozyten verbesserte bereits 1/4 × MHK von Clindamycin bzw. Linkomycin deutlich die leukozytäre Abtötung vonS. aureus, während beiS. epidermidis beide Substanzen die hohe leukozytäre Abtötungsrate auch bei inhibitorischen Konzentrationen nicht weiter verbessern konnten. In Hank's Medium mit Leukozyten allein hatten Clindamycin wie Linkomycin gegen beide Teststämme maximal nur einen bakteriostatischen Effekt.

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Antibacterial activity of clindamycin and lincomycin in broth, serum and in combination with polymorphonuclear leukocytes against staphylococcus aureus and staphylococcus epidermidis

Summary We investigated the antibacterial activity of clindamycin and lincomycin at 1/4×minimum inhibitory concentration (MIC), 1 × MIC and 4 × MIC against a serum-resistantStaphylococcus aureus and a serum-resistantStaphylococcus epidermidis strain in broth, in serum with and without the presence of leukocytes and in Hank's medium in combination with leukocytes alone. Against both test strains, lincomycin in broth and serum was similiarly effective, whereas againstS. aureus clindamycin in broth was somewhat more active. In the combined test mixture of serum with leukocytes, even a 1/4 × MIC of clindamycin or lincomycin markedly improved leukocyte killing ofS. aureus, whereas both compounds could not further enhance the marked leukocyte killing ofS. epidermidis, even at inhibitory concentrations. In Hank's medium with leukocytes alone, clindamycin and lincomycin had at the most only a bacteriostatic effect against both test strains.

     

Increased incidence of side effects after encainide: a newly developed antiarrhythmic drug

In a clinical trial the efficacy of encainide, a newly developed class I antiarrhythmic agent, was compared with the well-known mexiletine. Nine patients with different underlying cardiac disease and chronic complex ventricular ectopies (documented by 24-h Holter monitoring, confirmed during the initial placebo period) entered the study. The dosage of encainide was increased from 25 to 75 mg three times daily and the antiarrhythmic effect monitored by repeated 24-h Holter registration and in some patients by treadmill exercise testing. During the clinical followup we noted a high incidence of so-called "minor side effects" (headache, dizziness, blurred vision, tremor, and nausea), which caused us to terminate the study. In all instances adverse effects emerged before ectopic activity was suppressed satisfactorily prohibiting further increment of dosage. These results indicate that encainide cannot be regarded as an antiarrhythmic drug of first choice in routine clinical application.     

Influence of trait anxiety on inhibitory control in alcohol-dependent patients: simultaneous acquisition of ERPs and BOLD responses

Alcohol-dependence is often associated with comorbid psychiatric symptoms. However, the results concerning the influence of these symptoms on cognitive functioning in alcoholism are still inconsistent. The aim of this study was to determine performance monitoring in healthy volunteers and alcohol-dependent patients, and to assess the influence of trait anxiety on these processes. Sixteen healthy volunteers and 16 detoxified alcohol-dependent patients completed an auditory go/nogo paradigm. Functional magnetic resonance imaging, event-related potentials and behavioral data were acquired simultaneously. The patients were classified by median split based on level of self-rated trait anxiety (state-trait anxiety inventory; STAI). The results showed no significant differences regarding inhibition-associated electrophysiological and behavioral responses between alcohol-dependent patients with high-trait anxiety scores and alcohol-addicts with low-STAI scores. However, the functional MRI data revealed elevated activations during the response inhibition task especially in the middle frontal gyrus (BA 6/9), the superior frontal gyrus (BA 6/8/9) and the right inferior frontal gyrus, as well as temporo-parietal brain regions in patients with high-trait anxiety compared to non-anxious alcohol-addicts. Patients and healthy controls showed comparable results with regard to neural and behavioral responses. These results suggest that inhibitory control capacities of alcohol-dependent patients are not consistent: alcohol-addicts with high-trait anxiety ratings showed elevated neural responses compared to patients without any comorbid psychiatric symptoms. This may indicate that comorbid psychiatric symptoms need to be considered when assessing brain responses in alcohol-dependent patients.     

Coronary reperfusion studies with pro-urokinase in acute myocardial infarction: evidence for synergism of low dose urokinase

Pro-urokinase is a single chain precursor of two chain urokinase, which has been shown to induce fibrin-selective plasminogen activation. In the present study, thrombolytic efficacy of 9 million U of glycosylated pro-urokinase administered intravenously was compared with that of a combined regimen utilizing 4.5 million U of pro-urokinase and 0.2 million U of urokinase. Seventy-five patients with a first myocardial infarction were randomized to receive high dose pro-urokinase (n = 40, group A) or the combination therapy (n = 35, group B). Reperfusion of the infarct-related artery was assessed by repeat coronary angiography. Thrombolysis in Myocardial Infarction trial (TIMI) grade II or III reperfusion was achieved in 73% of group A patients compared with 66% of group B patients (p = NS). A trend toward faster reopening of the infarct-related artery was observed in patients in group B. Coronary artery reocclusion occurred in 5 (10%) of 49 patients in whom angiography was repeated within 36 h after the start of therapy. Clot-selective thrombolysis was indicated by a minimal fibrinogen decline (15% and 13%, respectively, in groups A and B). Alpha 2-antiplasmin levels, however, decreased more rapidly in patients in group B (p less than 0.05). This finding and the equivalent reperfusion rate in the combined treatment group strongly suggest synergistic interaction between these two thrombolytic agents. In summary, the high incidence of reperfusion, the low rate of early reocclusion and the paucity of side effects, particularly with regard to bleeding complications, indicate that pro-urokinase possesses the characteristics of an ideal thrombolytic agent.     

Impact of Intraoperative Radiotherapy on Cosmetic Outcome and Complications after Oncoplastic Breast Surgery

Breast cancer is one of the most common tumors in the population worldwide. Conservative breast surgery (CBS) is one of the preferred surgical options, because both the oncologic and esthetic needs of the patient can be addressed. CBS surgical outcomes tend to be more effective with reduced chances of disease recurrence when radiotherapy (RT) treatment is considered as an adjunct treatment, either applied during surgery (IORT) and/or after (EBRT). The purpose of our study was to compare surgical outcomes between IORT and EBRT after CBS. In the past 5 years, we performed CBS in 489 patients in our clinic. Of these patients, 83 underwent adjunct treatment with IORT and 109 were treated with EBRT in accordance with our university approved clinical protocol. Surgical outcomes, early complication rates, and esthetic results were compared between these two groups of CBS patients, with a mean follow‐up time of 17 months. IORT allowed breast irradiation treatment to be performed without effecting overlying skin, thus cosmetic outcomes tended to be favorable. Esthetic postoperative results assessed with the Breast Cancer Conservation Treatment (BCCTcore) software showed that the differences between IORT and EBRT were not statistically significant (including those patients that underwent further oncoplastic techniques after EBRT). The disease recurrence rates between the two groups were not significantly different. IORT is a safe, fast, and feasible technique that provides effective and comparable CBS outcomes for patients with breast cancer.     

Fully adiabatic 31P 2D‐CSI with reduced chemical shift displacement error at 7 T — GOIA‐1D‐ISIS/2D‐CSI

A fully adiabatic phosphorus (³¹P) two‐dimensional (2D) chemical shift spectroscopic imaging sequence with reduced chemical shift displacement error for 7 T, based on 1D‐image‐selected in vivo spectroscopy, combined with 2D‐chemical shift spectroscopic imaging selection, was developed. Slice‐selective excitation was achieved by a spatially selective broadband GOIA‐W(16,4) inversion pulse with an interleaved subtraction scheme before nonselective adiabatic excitation, and followed by 2D phase encoding. The use of GOIA‐W(16,4) pulses (bandwidth 4.3–21.6 kHz for 10–50 mm slices) reduced the chemical shift displacement error in the slice direction ～1.5–7.7 fold, compared to conventional 2D‐chemical shift spectroscopic imaging with Sinc3 selective pulses (2.8 kHz). This reduction was experimentally demonstrated with measurements of an MR spectroscopy localization phantom and with experimental evaluation of pulse profiles. In vivo experiments in clinically acceptable measurement times were demonstrated in the calf muscle (nominal voxel volume, 5.65 ml in 6 min 53 s), brain (10 ml, 6 min 32 s), and liver (8.33 ml, 8 min 14 s) of healthy volunteers at 7 T. High reproducibility was found in the calf muscle at 7 T. In combination with adiabatic excitation, this sequence is insensitive to the B₁ inhomogeneities associated with surface coils. This sequence, which is termed GOIA‐1D‐ISIS/2D‐CSI (goISICS), has the potential to be applied in both clinical research and in the clinical routine. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.